This program is designed to further our understanding of renal structure and function in health and disease. Specifically, changes of proximal and distal tubular function and structure will be evaluated in several experimental settings in dogs or rats utilizing renal micropuncture, microperfusion and standard clearance techniques, and light and electron microscopy. In healthy animals, particular emphasis will be directed toward an assessment of the nature and control of sodium and water reabsorption by the renal tubules, the relationship between the intrarenal redistribution of glomerular filtrate and blood flow and changes of renal sodium excretion, molecular transport properties of the isolated perfused tubule, and the influence of parathyroid hormone on the renal tubular reabsorption of bicarbonate. In dogs with an induced form of glomerulonephritis, special attention will be directed toward an investigation of renal mechanisms of sodium excretion, diuretic action and alterations of renal tubular function in severe renal disease. Furthermore, in dogs and rats with experimental obstructive uropathy, clearance and micropuncture studies will be designed to study the pathogenesis and mechanism of postobstructive diuresis in this disorder. Lastly, in patients with severe renal failure, the relationship between hypertensive conditions and alterations of plasma renin activity will be studied. Overall, the results of the program can be expected to further our knowledge of renal function in human conditions associated with alterations of renal function, edema formation, hypertension, the use of diuretic drugs, etc.